Cuproptosis has been implicated in lung adenocarcinoma (LUAD), but whether it contributes to the biological functions of ATPase copper transporting alpha (ATP7A) and lipoic acid synthetase (LIAS) remains unclear. This study aimed to investigate the roles of ATP7A and LIAS in LUAD progression and their association with cuproptosis-related alterations. ATP7A and LIAS expression was assessed in LUAD-related human tissues (n = 20 per group) and LUAD cell lines (A549 and PC9) by RT-qPCR, western blotting, and immunohistochemistry. Gain- and loss-of-function experiments were used to evaluate cell proliferation, migration, and epithelial–mesenchymal transition (EMT) (CCK-8, wound-healing, and Transwell assays, with molecular analyses). Cuproptosis-related changes were assessed using FDX1 expression, pyruvate and α-ketoglutarate levels, mitochondrial ultrastructure, and lipoylation-related readouts. Nude mouse subcutaneous xenografts were used for in vivo validation, with an additional independent cohort for Ki-67 immunohistochemistry and TUNEL staining. ATP7A and LIAS were significantly upregulated in LUAD tissues and cell lines compared with controls (all p 0.05). In vivo, ATP7A or LIAS knockdown suppressed xenograft tumor growth (p < 0.01), with reduced Ki-67 staining and increased TUNEL positivity in the independent validation cohort (both p < 0.01). ATP7A and LIAS promote LUAD progression and are associated with cuproptosis-related alterations, supporting a role for ATP7A/LIAS-regulated cuproptosis-related pathways in LUAD.
Liu et al. (Wed,) studied this question.